This application is for a five-year renewal of the study entitled, "Prevention of Alzheimer's Disease by Vitamin E and Selenium" (PREADVISE). PREADVISE is an add-on study to the Selenium and Vitamin E Prostate Cancer Prevention Trial (SELECT), a National Cancer Institute funded phase III, double blind, 2x2 factorial randomized control trial to assess the effect of Se or vitamin E or the combination of both on the reduction of the incidence of prostate cancer in 35,534 healthy men. The study duration is 12 years. Prevention is the key to eliminating Alzheimer's disease (AD). Multiple studies have demonstrated that oxidative damage to lipids, proteins, DMA, and RNA plays a role in the pathogenesis of neurodegeneration in AD. Recent studies have shown that marked oxidative damage is present in mild cognitive impairment, the earliest detectable form of the disease. Population studies also suggest using antioxidants for AD prevention and underscore the need for large scale, long term, randomized controlled trials of antioxidants in AD. Thus, the rationale for diminishing oxidative stress/damage as a means of slowing the onset or preventing AD is on a solid basis. The aims of PREADVISE are to define the effect of Se and/or vitamin E on the reduction of the incidence of AD and other neurodegenerative diseases, and to assess the effect of Se and vitamin E on normal cognitive aging in a sub-sample of participants. Also during this five year phase, emphasis will be placed on retention of subjects in PREADVISE and SELECT. PREADVISE has recruited 5,100 participants and 18% of these are ethnic minorities. Another 1,300 men are eligible for enrollment in PREADVISE. PREADVISE subjects are randomized to one of four arms:vitamin E plus Se, vitamin E plus Se placebo, Se plus vitamin E placebo, and Se placebo plus vitamin E placebo. Participants undergo a memory impairment screening examination as part of the initial evaluation and annuallly thereafter. Those that fall below the cut off point undergo a more thorough cognitive evaluation using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Subjects who fail the CERAD battery receive a thorough dementia evaluation that is reviewed by a consensus conference. DNA is available for APOE genotype testing and future study of other genetic factors in AD. This is the largest national and international prevention trial of AD and is based on an innovative and inter-institute collaborative sub-study model that is uniquely cost effective